DESCRIPTION: (Adapted from the application) Shahin Lockman, M.D. has completed an Infectious Diseases fellowship at Massachusetts General/Brigham and Women's Hospitals in Boston and a two-year Epidemic Intelligence Service program at the Centers for Disease Control Division of Tuberculosis (TB) Elimination. In this latter capacity she helped to plan and execute multiple studies pertaining to the epidemiology of TB and HIV in Botswana and Estonia. She will work with Dr. Max Essex on clinical trials studying approaches to perinatal HIV transmission prevention in Botswana, as well as studies of other aspects of HIV epidemiology and infant infectious disease morbidity and mortality. The candidate plans to pursue an independent career in HIV and TB epidemiology and clinical trials. HIV-I prevalence among women of child-bearing age in Botswana is 28-43%, and greater than 33% of infants born to these women are likely to be infected. Seven to 22% of HIV-infected women may transmit HIV to their infants via breast milk; breast-feeding is widely practiced throughout sub-Saharan Africa. The critical question of rates of overall mortality and infectious disease morbidity among infants of HIV-positive mothers who are breast-fed while receiving prophylactic antiretrovirals versus those who are formula-fed has not been answered. Acute respiratory infection is a leading cause of Infant morbidity and mortality in the developing world, the etiology and outcome of respiratory disease and bloodstream infection in HIV-infected infants in sub- Saharan Africa have not been evaluated prospectively, nor have they been compared between breast- and formula-feeding infants in this setting. Answers to these questions would be of value to clinicians and to national health policy-makers. Finally, the efficacy and safety of antenatal/intrapartum ZDV versus the same regimen plus short-course nevirapine have not been studied in pregnant HIV-infected mothers and their infants. The primary study objectives are to determine the efficacy and safety of ZDV given for 6 months to infants born to HIV-infected mothers for reducing HIV-I subtype C transmission by breast-feeding compared with formula-feeding, and to study the efficacy of ZDV versus ZDV plus short-course nevirapine in preventing mother-to-infant HIV transmission. Other objectives Include evaluating (a) etiology and outcome of infant respiratory disease and bloodstream infection in Botswana, and ascertaining any protective effect of breast milk on respiratory disease morbidity and mortality, (b) decision analysis of the most efficacious feeding strategy for infants of HIV-positive mothers, comparing breast-feeding, with prophylactic infant ZDV and formula-feeding and (c) HIV-I viral phenotypes and genotypes/drug resistance mutations in HIV-infected infants treated with ZDV. The candidate will be a principal investigator on (a) and (b), and will assist with achieving all other study objectives. The study will be carried out in 3 towns in southeast Botswana as a collaborative effort between the Harvard AIDS Institute and the AIDS/STD Unit of Botswana. Baseline rates of transmission are being ascertained from HIV-infected mothers (and their infants) who have already delivered. The proposed intervention will involve HIV-infected consenting pregnant women, and will consist of giving: 1) all women ZDV from 34 weeks of gestation to one week post-partum- one half of the mothers and infants will each receive one dose of intrapartum/post-partum nevirapine, and the other half will receive placebo, and 2) one half of infants will be randomized to formula-feeding and the other half to breast-feeding plus ZDV for 6 months. In addition, Dr. Lockman will compare the rates, etiologies, and outcomes of respiratory disease, bloodstream infection, and nasopharyngeal colonization with pathogens between the breast-feeding and formula-feeding infants, stratified by HIV status, and will perform a decision analysis evaluating optimal infant feeding strategy in Botswana and in similar settings with high HIV prevalence and relatively high infant mortality rates from other infectious diseases.